Traumatic brain injury (TBI) is the most common cause of death in childhood. Extra-axial hemorrhage (EAH, which includes subdural and subarachnoid hemorrhage) carries additional medical-legal significance, as it is often used to distinguish between accidental and abusive injury etiologies in young children. Although EAH is generally thought to occur from tearing of bridging veins (BVs) and/or cortical vessels, there is a paucity of data about the age dependence of BV properties, as well as the relationship between number of vessels ruptured and extent of EAH. In this proposal to investigate TBI mechanisms specific to young children, our hypotheses are that rapid rotations of the immature head can produce BV failure, that the biomechanical BV properties of the infant will reveal lower BV rupture stress and strain than the adult, conferring a vulnerability for BV rupture to the infant. n addition, we hypothesize that cyclic elongation will soften the BVs, rendering them more fragile with repeated head rotations than single events. With expertise in biomechanical testing and finite element analysis, and archived data from patient studies, animal experiments and anthropomorphic doll simulations of accidental and abusive TBI events, we are uniquely poised to determine the mechanisms associated with EAH in TBI. In this exploratory R21 grant application, our 2-year goal is to leverage these previous discoveries with new experiments to identify the mechanisms of traumatic EAH in children. In just two years, we will be the first to determine mechanical properties of pediatric BVs (Aim 1);integrate them into computational finite element models (FEMs) for EAH prediction, and validate the predictive capabilities of our procedures (Aim 2);and use the FEMs to identify EAH potential in single and cyclic head movements (Aim 3). Taken together, the results of this basic research plan will provide the scientific foundation for the development of new strategies for injury prevention, clinical diagnosis, and injury mitigation to reduce the number of children with new debilitating TBIs each year.

Public Health Relevance

Traumatic brain injury (TBI) is the most common cause of death in childhood. Leveraging our expertise in tissue testing, large animal experiments, human studies, anthropomorphic dummies, and finite element models, our objective is to deepen our mechanistic understanding of traumatic bridging failure and extra-axial hemorrhage in the developing brain. The results of this basic research plan will provide the scientific foundation fo the future development of new strategies for injury prevention, clinical diagnosis, and injury mitigation, targeted to reduce serious TBIs in children.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD078842-01A1
Application #
8769696
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Maholmes, Valerie
Project Start
2014-08-08
Project End
2016-07-31
Budget Start
2014-08-08
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$234,682
Indirect Cost
$84,682
Name
University of Pennsylvania
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104